U.S. patent application number 12/917236 was filed with the patent office on 2011-04-07 for treatment of clinical applications with neuromodulation.
Invention is credited to David J. Mishelevich, M. Bret Schneider.
Application Number | 20110082326 12/917236 |
Document ID | / |
Family ID | 43823710 |
Filed Date | 2011-04-07 |
United States Patent
Application |
20110082326 |
Kind Code |
A1 |
Mishelevich; David J. ; et
al. |
April 7, 2011 |
TREATMENT OF CLINICAL APPLICATIONS WITH NEUROMODULATION
Abstract
Described herein are systems and methods for Transcranial
Magnetic Stimulation (TMS) including one or more TMS electromagnets
for stimulation of target deep brain regions to stimulate, enhance
and/or inhibit neural activity.
Inventors: |
Mishelevich; David J.;
(Playa del Rey, CA) ; Schneider; M. Bret; (Portola
Valley, CA) |
Family ID: |
43823710 |
Appl. No.: |
12/917236 |
Filed: |
November 1, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12402404 |
Mar 11, 2009 |
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12917236 |
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10821807 |
Apr 9, 2004 |
7520848 |
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12402404 |
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11429504 |
May 5, 2006 |
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10821807 |
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61256480 |
Oct 30, 2009 |
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Current U.S.
Class: |
600/13 ;
600/15 |
Current CPC
Class: |
A61N 2/006 20130101;
A61N 2/02 20130101 |
Class at
Publication: |
600/13 ;
600/15 |
International
Class: |
A61N 2/02 20060101
A61N002/02 |
Claims
1. A method of treating a disorder by non-invasive neural
stimulation, the method comprising modulating the activity of the
majority of a target deep-brain region, wherein the target brain
region is selected from the group consisting of: neocortex, medial
PFC, LDLPFC, RDLPFC, dorsomedial PFC, ventral PFC, VMPFC,
orbitofrontal cortex (OFC), tracts between OFC and insula,
cingulate genu, DACG, Pre-Gen. anterior cingulate, subgenual
cingulate, posterior cingulate, striatum-DACG connections, tracts
between pre-gen, anterior cingulate and insula, insula, amygdala,
anterior limb of internal capsule, ventral internal capsule,
target, nucleus accumbens, tract between nucleus acumbens and
ventral teg., hippocampus, temporal lobes, septum, caudate
(nucleus), globus pallidus, anterior nucleus of the thalamus,
lateral thalamus, centromedian thalamus, thalamic subregions,
subthalamic nucleus, lateral hypothalamic area nuclei, ventromedial
nuclei of hypothal., cerebellum, brainstem, and pons.
2. The method of claim 1, wherein the step of modulating the
activity comprises up-regulating the activity of the target
region.
3. The method of claim 1, wherein the step of modulating the
activity comprises down-regulating the activity of the target
region.
4. The method of claim 1, wherein the step of modulating the
activity comprises non-invasively stimulating the target region to
modulate the activity using an array of TMS electromagnets.
5. The method of claim 1, wherein the step of modulating the
activity of the target region does not substantially modulate the
activity of non-target brain regions.
6. The method of claim 1, wherein the step of modulating the
activity comprises applying energy to activate an array of TMS
electromagnets.
7. The method of claim 1, further comprising positioning an array
of TMS electromagnets to modulate each of the target brain
regions.
8. The method of claim 1, wherein the disorder is selected from the
group consisting of: addiction, Alzheimer's disease, anogasmia,
attention deficit disorder, autism, cerebral palsy, depression,
bipolar, depression, unipolar, epilepsy, generalized anxiety
disorder, head trauma (acute), hedonism, obesity, OCD, acute pain,
chronic pain, Parkinson's disease, persistent vegetative state,
phobia, PTSD, social anxiety disorder, rehab/regenesis for
post-stroke, post-head trauma, hemorrhagic stroke, ischemic stroke,
and Tourette's syndrome.
9. The method of claim 1, further comprising modulating the
activity of the majority of a second target brain region.
10. The method of claim 9, wherein the second target brain region
is modulated simultaneously with the modulation of the first target
brain region.
11. The method of claim 1, wherein the step of modulating the
activity is performed by moving at least one TMS coil around a
subject's head to stimulate the target brain region.
12. A method of treating a disorder by non-invasive neural
stimulation, the method comprising simultaneously modulating the
activity of two or more target brain regions to up-regulate or
down-regulate activity in the target brain region, wherein the
target brain regions are selected from the group consisting of:
NeoCortex, Medial PFC, LDLPFC, RDLPFC, Dorsomedial PFC, Ventral
PFC, VMPFC, Orbitofrontal Cortex (OFC), Tracts between OFC and
Insula, Cingulate Genu, DACG, Pre-Gen. Anterior Cingulate,
Subgenual Cingulate, Posterior Cingulate, Striatum-DACG
Connections, Tracts between Pre-Gen. Anterior Cingulate and Insula,
Insula, Amygdala, Anterior Limb of Internal Capsule, Ventral
Internal Capsule, Target, Nucleus Accumbens, Tract between Nucleus
Acumbens and Ventral Teg., Hippocampus, Temporal Lobes, Septum,
Caudate (Nucleus), Globus Pallidus, Anterior Nucleus of the
Thalamus, Lateral Thalamus, Centromedian Thalamus, Thalamic
Subregions, Subthalamic Nucleus, Lateral Hypothalamic Area Nuclei,
Ventromedial Nuclei of Hypothal., Cerebellum, Brainstem, and
Pons.
13. The method of claim 12, wherein the step of simultaneously
modulating activity comprises modulating the activity in the
majority of the target brain regions.
14. The method of claim 12, wherein the step of simultaneously
modulating activity comprises non-invasively stimulating.
15. The method of claim 12, wherein the step of simultaneously
modulating activity comprises stimulating by deep-brain TMS.
16. The method of claim 12, wherein the step of simultaneously
modulating activity comprises up-regulating activity in one target
brain region.
17. The method of claim 12, wherein the step of simultaneously
modulating activity comprises down-regulating activity in one
target brain region.
18. The method of claim 12, wherein the step of simultaneously
modulating activity comprises up-regulating activity in one target
brain region while down-regulating activity in another brain
region.
19. The method of claim 12, wherein the step of simultaneously
modulating activity does not substantially modulate the activity of
non-target brain regions.
20. The method of claim 12, wherein the step of simultaneously
modulating the activity comprises applying energy to activate one
or more arrays of TMS electromagnets.
21. The method of claim 12, further comprising positioning one or
more arrays of TMS electromagnets to modulate each of the target
brain regions.
22. The method of claim 12, wherein the disorder is selected from
the group consisting of: addiction, Alzheimer's disease, anogasmia,
attention deficit disorder, autism, cerebral palsy, depression,
bipolar, depression, unipolar, epilepsy, generalized anxiety
disorder, head trauma (acute), hedonism, obesity, OCD, acute pain,
chronic pain, Parkinson's disease, persistent vegetative state,
phobia, PTSD, social anxiety disorder, rehab/regenesis for
post-stroke, post-head trauma, hemorrhagic stroke, ischemic stroke,
and Tourette's syndrome.
23. A method of treating hedonic disorders by non-invasive neural
stimulation, the method comprising applying energy to modulate
activity of the Orbitofrontal Cortex (OFC).
24. The method of claim 23, wherein the hedonic disorder is
selected from the group consisting of: addiction, sexual disorders,
and eating disorders.
25. The method of claim 23 wherein the step of applying energy to
modulate the activity of the OFC comprises stimulating the OFC to
suppress activity.
26. The method of claim 23, wherein the step of applying energy to
modulate the activity of the OFC comprises simultaneously
stimulating the majority of the OFC.
27. The method of claim 23, wherein the step of applying energy to
modulate the activity of the OFC comprises stimulating the OFC
without substantially modulating neural activity in other brain
regions including those adjacent to the OFC.
28. A method of treating obesity by non-invasive neural
stimulation, the method comprising applying energy to modulate the
activity of the Orbitofrontal Cortex (OFC).
29. The method of claim 28, wherein the step of applying energy to
modulate comprises non-invasively stimulating the OFC with at least
one TMS electromagnet.
30. The method of claim 28, wherein the step of applying energy to
modulate comprises simultaneously stimulating the majority of the
OFC.
31. The method of claim 28, wherein the step of applying energy to
modulate comprises stimulating the OFC with an array of TMS
electromagnets.
32. The method of claim 28, further comprising arranging an array
of TMS electromagnets to target the OFC.
33. The method of claim 28, further comprising emitting energy from
an array of TMS electromagnets to focus the emitted energy on the
OFC.
34. The method of claim 28, wherein the step of applying energy to
modulate comprises inhibiting or suppressing activity of the
OFC.
35. A method of treating addiction by non-invasive neural
stimulation, the method comprising simultaneously applying energy
to modulate the activity of two or more target brain regions
selected from the group consisting of: the insula, the
Orbitofrontal Cortex (OFC), the tracts between the OFC and the
Insula, and the DACG.
36. A method of treating depression by non-invasive neural
stimulation, the method comprising simultaneously applying energy
to modulate the activity of two or more target brain regions
selected from the group consisting of: the LDLPFC, the RDLPFC, the
DACG, and the Orbitofrontal Cortex (OFC).
37. A method of treating pain by non-invasive neural stimulation,
the method comprising simultaneously applying energy to modulate
the activity of two or more target brain regions selected from the
group consisting of: the Cingulate Gyms, the DACG, the Insula and
the Lateral Thalamus.
38. The method of any of claim 35, wherein the step of
simultaneously applying energy to modulate the activity comprises
non-invasively stimulating using at least one TMS
electromagnet.
39. The method of any of claim 36, wherein the step of
simultaneously applying energy to modulate the activity comprises
non-invasively stimulating using at least one TMS
electromagnet.
40. The method of any of claim 37, wherein the step of
simultaneously applying energy to modulate the activity comprises
non-invasively stimulating using at least one TMS
electromagnet.
41. The method of any of claim 35, wherein the step of
simultaneously applying energy to modulate the activity comprises
simultaneously stimulating the majority of the target brain
regions.
42. The method of any of claim 36, wherein the step of
simultaneously applying energy to modulate the activity comprises
simultaneously stimulating the majority of the target brain
regions.
43. The method of any of claim 37, wherein the step of
simultaneously applying energy to modulate the activity comprises
simultaneously stimulating the majority of the target brain
regions.
44. The method of any of claim 35, wherein the step of
simultaneously applying energy to modulate activity comprises
stimulating by TMS using a plurality of TMS electromagnets.
45. The method of any of claim 36, wherein the step of
simultaneously applying energy to modulate activity comprises
stimulating by TMS using a plurality of TMS electromagnets.
46. The method of any of claim 37, wherein the step of
simultaneously applying energy to modulate activity comprises
stimulating by TMS using a plurality of TMS electromagnets.
47. The method of any of claim 35, wherein the step of
simultaneously applying energy to modulate activity comprises
up-regulating activity in one target brain region.
48. The method of any of claim 36, wherein the step of
simultaneously applying energy to modulate activity comprises
up-regulating activity in one target brain region.
49. The method of any of claim 37, wherein the step of
simultaneously applying energy to modulate activity comprises
up-regulating activity in one target brain region.
50. The method of any of claim 35, wherein the step of
simultaneously applying energy to modulate activity comprises
down-regulating activity in one target brain region.
51. The method of any of claim 36, wherein the step of
simultaneously applying energy to modulate activity comprises
down-regulating activity in one target brain region.
52. The method of any of claim 37, wherein the step of
simultaneously applying energy to modulate activity comprises
down-regulating activity in one target brain region.
53. The method of any of claim 35, wherein the step of
simultaneously applying energy to modulate activity comprises
up-regulating activity in one target brain region while
down-regulating activity in another brain region.
54. The method of any of claim 36, wherein the step of
simultaneously applying energy to modulate activity comprises
up-regulating activity in one target brain region while
down-regulating activity in another brain region.
55. The method of any of claim 37, wherein the step of
simultaneously applying energy to modulate activity comprises
up-regulating activity in one target brain region while
down-regulating activity in another brain region.
56. The method of any of claim 35, wherein the step of
simultaneously applying energy to modulate activity does not
substantially modulate the activity of non-target brain
regions.
57. The method of any of claim 36, wherein the step of
simultaneously applying energy to modulate activity does not
substantially modulate the activity of non-target brain
regions.
58. The method of any of claim 37, wherein the step of
simultaneously applying energy to modulate activity does not
substantially modulate the activity of non-target brain
regions.
59. The method of any of claim 35, further comprising positioning
one or more arrays of TMS electromagnets to modulate each of the
target brain regions.
60. The method of any of claim 36, further comprising positioning
one or more arrays of TMS electromagnets to modulate each of the
target brain regions.
61. The method of any of claim 37, further comprising positioning
one or more arrays of TMS electromagnets to modulate each of the
target brain regions.
62. A method of treating a disorder by targeted deep-brain
Transcranial Magnet Stimulation of a neuronal circuit associated
with the disorder, the method comprising: identifying a plurality
of target brain regions from a neuronal circuit associated with the
neuronal disorder; aiming a plurality of TMS electromagnets at each
of the target brain regions, wherein at least one of the target
brain regions comprises a deep brain target; and applying power to
the TMS electromagnets to modulate the activity of the target brain
regions.
63. The method of claim 62, wherein the disorders treated are
selected from the group consisting of: addiction, Alzheimer's
disease, anogasmia, Attention Deficit Disorder, autism, cerebral
palsy, bipolar depression, unipolar depression, epilepsy,
generalized anxiety disorder, head trauma (acute), hedonism,
obesity, OCD, acute pain, chronic pain, Parkinson's disease,
persistent vegetative state, phobia, PTSD, social anxiety disorder,
post-stroke and post-heat trauma rehabilitation/regenesis,
Hemorrhagic stroke, ischemic stroke, and Tourette's syndrome.
64. The method of claim 62, wherein the step of aiming comprises
simultaneously aiming the TMS electromagnets at each of the target
brain regions.
65. The method of claim 62, wherein the step of aiming comprises
determining positions and orientation for each of the plurality of
TMS electromagnets based on the target and one or more of an atlas,
brain imaging, or external landmarks on head.
66. A method of treating addiction by targeted deep-brain
Transcranial Magnet Stimulation, the method comprising: targeting
one or more TMS electromagnets at each of two or more of the
targets selected from the list comprising: the Orbitofrontal Cortex
(OFC), the tracts between the OFC and the Insula, the DACG, the
Medial PFC, the Striatum-DACG connections, the anterior limb of the
internal capsule, and the Insula; and applying power to the one or
more TMS electromagnets to modulate the activity of the targeted
brain regions to treat addiction.
67. A method of treating obesity by targeted deep-brain
Transcranial Magnet Stimulation, the method comprising: targeting
one or more TMS electromagnets at each of two or more of the
targets selected from the list comprising: the Orbitofrontal Cortex
(OFC), the Insula, the lateral hypothalamic area nuclei, and the
ventromedial nuclei of the hypothalamus; and applying power to the
one or more TMS electromagnets to modulate the activity of the
targeted brain regions to treat obesity.
68. A method of treating pain by targeted deep-brain Transcranial
Magnet Stimulation, the method comprising: targeting one or more
TMS electromagnets at each of two or more of the targets selected
from the list comprising: the cingulate gyrus, the DACG, the Insula
and the lateral thalamus; and applying power to the one or more TMS
electromagnets to modulate the activity of the targeted brain
regions to treat pain.
69. A method of treating depression by targeted deep-brain
Transcranial Magnet Stimulation, the method comprising: targeting
one or more TMS electromagnets at each of two or more of the
targets selected from the list comprising: the LDLPFC, the RDLPFC,
the Orbitofrontal Cortex (OFC), and the subgenual cingulate; and
applying power to the one or more TMS electromagnets to modulate
the activity of the targeted brain regions to treat depression.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This patent application claims priority as a
continuation-in-part of U.S. patent application Ser. No.
12/402,404, filed Mar. 11, 2009 and titled "ROBOTIC APPARATUS FOR
TARGETING AND PRODUCING DEEP, FOCUSED TRANSCRANIAL MAGNETIC
STIMULATION," which is a divisional of U.S. patent application Ser.
No. 10/821,807, filed Apr. 9, 2004, now U.S. Pat. No. 7,520,848 and
titled "ROBOTIC APPARATUS FOR TARGETING AND PRODUCING DEEP, FOCUSED
TRANSCRANIAL MAGNETIC STIMULATION."
[0002] This patent application also claims priority as a
continuation-in-part to U.S. patent application Ser. No.
11/429,504, filed on May 5, 2006 and titled "TRAJECTORY-BASED
DEEP-BRAIN STEREOTACTIC TRANSCRANIAL MAGNETIC STIMULATION".
[0003] This application also claim priority to provisional patent
application Ser. No. 61/256,480, filed on Oct. 30, 2009 and titled
"TREATMENT OF CLINICAL APPLICATIONS WITH NEUROMODULATION." The
disclosures of each of these patent applications are herein
incorporated by reference in their entirety.
INCORPORATION BY REFERENCE
[0004] All publications and patent applications mentioned in this
specification are herein incorporated by reference in their
entirety to the same extent as if each individual publication or
patent application was specifically and individually indicated to
be incorporated by reference.
FIELD OF THE INVENTION
[0005] Described herein are systems and methods for Transcranial
Magnetic Stimulation (TMS) including one or more TMS electromagnets
for stimulation of target deep brain regions to stimulate, enhance
and/or inhibit neural activity.
BACKGROUND OF THE INVENTION
[0006] A variety of techniques have been developed for
neuromodulation of neural structures, including Transcranial
Magnetic Stimulation (TMS), Deep Brain Stimulation (DBS), open
surgery, Stereotactic Radiosurgery, transcranial Direct Current
Simulation (tDCS), and ultra sound. There are functional as well as
technical differences between these different modalities. For
example, stereotactic Transcranial Magnetic Stimulation (sTMS)
allows direct neuromodulation of deep targets while traditional
repetitive Transcranial Magnetic Stimulation (rTMS) does not. Some
modalities are non-invasive, including TMS, ultrasound, tDCS, and
ionizing radiation. Other modalities are at least somewhat
invasive, including DBS, open surgery, surface electrodes,
optogenetic, and Stereotactic Radiosurgery. Examples of other
modalities are described in US 2009/0112133 and US
2009/0114849.
[0007] Further, some targets may be impractical for modulation with
a particular modality. For example, the Insula is believed to be
too vascular to allow treatment using traditional DBS. The
identification of suitable targets, both individually and as
elements of neural circuits, for a particular modality is of
fundamental importance. The identification of configurations
allowing treatment is of particular importance.
[0008] In particular, the stimulation of deep brain targets, of
combinations of neuronal targets including deep brain targets, of
multiple superficial targets, and/or of combinations of superficial
and deep brain targets has traditionally been difficult or
impossible to achieve by Transcranial Magnetic Stimulation (TMS).
The methods, systems and devices for deep-brain stimulation using
TMS that we have previously described (see, e.g., the references
incorporated in their entirety above), may allow for specific and
meaningful targeting of such targets. Described below are systems,
devices and methods for modulating these targets in a manner that
was previously not possible.
SUMMARY OF THE INVENTION
[0009] Neuromodulation of target neural structures by up-regulating
or down-regulating their activity results in treatment of clinical
conditions/applications. Described herein are methods of
non-invasively modulating specific identified target structures
believed to be involved in neural circuits that may be
therapeutically important. In particular, described herein are
Transcranial Magnetic Stimulation (TMS) devices, systems and
methods for modulating these targets. In general, the TMS devices,
methods and systems described herein are configured to stimulate
deep brain targets (such as those referred to above) or
combinations of targets including deep brain targets.
[0010] These brain targets may comprise neural circuits, as
described in greater detail below. The targets (e.g., portions of
the circuit) may be discrete neuroanatomical regions (e.g., target
regions of the brain) that are groups of neurons that are organized
into anatomical bodies. Thus, the targets may be neuroanatomical
structures within the brain. Neuroanatomical structures may have
discrete functions and may be organized by morphology. Exemplary
neuroanatomic structures may include NeoCortex, Medial PFC, LDLPFC,
RDLPFC, Dorsomedial PFC, Ventral PFC, VMPFC, Orbitofrontal Cortex
(OFC), Tracts between OFC and Insula, Cingulate Genu, DACG,
Pre-Gen. Anterior Cingulate, Subgenual Cingulate, Posterior
Cingulate, Striatum-DACG Connections, Tracts between Pre-Gen.
Anterior Cingulate and Insula, Insula, Amygdala, Anterior Limb of
Internal Capsule, Ventral Internal Capsule, Target, Nucleus
Accumbens, Tract between Nucleus Acumbens and Ventral Teg.,
Hippocampus, Temporal Lobes, Septum, Caudate (Nucleus), Globus
Pallidus, Anterior Nucleus of the Thalamus, Lateral Thalamus,
Centromedian Thalamus, Thalamic Subregions, Subthalamic Nucleus,
Lateral Hypothalamic Area Nuclei, Ventromedial Nuclei of Hypothal.,
Cerebellum, Brainstem, and Pons.
[0011] The TMS systems described herein (which may also be referred
to as "deep-brain TMS systems") typically included electromagnetic
coils and/or coil arrays configured to treat clinical
applications.
[0012] As referred to herein, "up-regulation" (or "up") refers to
neuromodulation to increase the level of neural firing and/or
metabolic activity in the targeted brain region. Up-regulation is
usually accompanied by (or correlated with) an increase in blood
flow to the up-regulated region of the brain. In general,
up-regulation may mean an increase in action potentials fired in
the region up-regulated, as well as an increase in glucose
consumption. Down-regulation typically means the opposite of
up-regulation, and may mean suppression of metabolic activity in
the region. Thus, in a down-regulated region there may be fewer
spontaneous action potential firings (i.e., a reduction in action
potential firings).
[0013] The tables shown in FIGS. 8 and 9 illustrate exemplary
application of up-regulation and down-regulation.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1A is a diagram of a neural circuit for addiction.
[0015] FIG. 1B is a diagram of a neural circuit for pain.
[0016] FIG. 2 is a diagram of a neural circuit for depression.
[0017] FIG. 3 is a diagram of a neural circuit for obesity.
[0018] FIG. 4 is a diagram of a neural circuit for Obsessive
Compulsive Disorder (OCD).
[0019] FIGS. 5, 6, and 7 illustrate a selected set of
electromagnetic coil configurations.
[0020] FIGS. 8 and 9 illustrate selected applications mapped onto
targets and associated electromagnetic coil configurations which
may be used in their treatment as described herein.
[0021] FIG. 10 is a table of three alternative coil configurations
for the treatment of Addiction.
[0022] FIG. 11 is a table of four alternative coil configurations
for the treatment of depression.
[0023] FIG. 12 is a table of three alternative coil configurations
for the treatment of pain.
[0024] FIG. 13 is a CAD illustration of one variation of TMS
electromagnets configured to treat Addiction.
[0025] FIG. 14 is a CAD illustration of another variation of TMS
electromagnets configured to treat Addiction.
[0026] FIG. 15 is a CAD illustration of another variation of TMS
electromagnets configured to treat Addiction.
[0027] FIG. 16 is a CAD illustration of one variation of TMS
electromagnets configured to treat depression.
[0028] FIG. 17 is a CAD illustration of another variation of TMS
electromagnets configured to treat depression.
[0029] FIG. 18 is a CAD illustration of another variation of TMS
electromagnets configured to treat depression.
[0030] FIG. 19 is a CAD illustration of another variation of TMS
electromagnets configured to treat depression.
[0031] FIG. 20 is a CAD illustration of one variation of TMS
electromagnets configured to treat pain.
[0032] FIG. 21 is a CAD illustration of another variation of TMS
electromagnets configured to treat pain.
[0033] FIG. 22 is a CAD illustration of another variation of TMS
electromagnets configured to treat pain.
[0034] FIG. 23 shows interdigitated figure-8 coils.
DETAILED DESCRIPTION OF THE INVENTION
[0035] In general, the systems, devices and methods described
herein and incorporated by reference may be used to treat one or
more clinical conditions. Although the methods, devices and systems
described herein are directed primarily to Transcranial Magnetic
Stimulation (TMS), some of the principles described herein may be
applied or adapted for use with other modalities, or in combination
with other modalities. For example, a particular clinical
application or condition may be impacted by a therapeutic modality
based on the impact of that modality on one or more neural targets.
This is true whether the modality is TMS, DBS, ultrasound,
stereotactic radiosurgery or other treatment.
[0036] Physiological functions and, if there are problems, clinical
conditions are usually not controlled by a single neural structure,
but a neural circuit. The circuit is typically made up of neural
structures (e.g., nuclei and tracts, gray matter, white matter,
etc.) each of which is a potential target for therapeutic
intervention. However, not all potential targets are practical
targets. A given potential target may be in accessible (e.g., too
deep to be reached by a given therapeutic modality), may have
critical structures that might be negatively impacted by a
therapeutic modality in close proximity and thus be too dangerous
to attempt, or may be impractical because targeting that structure
may physically prevent targeting a higher-priority structure.
[0037] For example, FIG. 1A shows a schematic diagram a neural
circuit for addiction. From this circuit, potential targets include
the Prefrontal Cortex, Orbitofrontal Cortex, Medial Prefrontal
Cortex, DACG, Subgenual Anterior Cingulate, Nucleus Accumbens,
Tract between the Nucleus Accumbens and Ventral Tegmentum, Insula,
and the Tract between the Insula, and the Orbitofrontal Cortex. A
subset of these targets may be chosen for therapy. Which subset is
practical will depend on the therapeutic modality.
[0038] As described in greater detail herein, stimulation of one or
more targets (including combinations of these targets) may be made
possible using the TMS devices and systems for deep brain
stimulation described herein in a way that would not otherwise be
possible by traditional TMS. FIG. 1B shows a similar neural circuit
for pain. In any of the neural circuit diagrams provided (e.g.,
FIGS. 1A-4), the two-dimensional arrows point toward targets that
may be modulated to treat a disorder affiliated with the
circuit.
[0039] FIG. 2 shows a neural circuit for depression. This neural
circuit suggests that potential targets include the Doral Anterior
Cingulate (Brodmann's Area 24), the Rostral Anterior Cingulate
(Brodmann's Area 24a), and the Subgenual Cingulate (Brodmann's Area
25).
[0040] Similarly, FIG. 3 shows a neural circuit for obesity. This
circuit shows a particular single potential target, the Lateral
Orbitofrontal Cortex. This target is of particular interest because
the Oribitofrontal Cortex is the final pathway for output of the
Lateral Hypothalamic Area where hunger sensation is transmitted. By
down-regulation of the Lateral Hypothalamic Area; perceived hunger
may be decreased. The same effect may be achieved by
down-modulation of the Oribito-Frontal Cortex target instead, a
target that is much more accessible and thus much easier to
stimulate.
[0041] FIG. 4 shows a neural circuit for OCD. Potential targets in
this circuit include the Ventral Prefrontal Cortex, the Anterior of
the Internal Capsule, and the Dorsal Anterior Cingulate.
[0042] The methods described herein include modulating multiple
targets in a particular neural circuit in order to affect a
clinical result. For example, hitting (modulating) multiple targets
in a neural circuit may facilitate Long-Term Potentiation (LTP) or
Long-Term Depression (LTD) and thus result in a more durable
treatment. Modulating a target typically means having energy reach
the target so that it is either up-regulated or down-regulated.
Modulation a target may also mean that the target structure is
modulated without substantially modulating non-target region. The
TMS systems described herein may be configured to hit (modulate)
multiple targets. Hitting multiple targets (particularly in a
coordinated manner) may improve therapeutic effectiveness by
modulating multiple points in the neural circuit, potentially
allowing the therapeutic effect to be achieved in a shorter period
of therapy time. While alternative therapeutic modalities may used
to hit multiple targets, some modalities may be less suitable to
hitting multiple targets. For example, using DBS to hit
Orbitofrontal Cortex, Dorsal Anterior Cingulate, and the Insula
simultaneously would be both very risky and very expensive. The
Insula, because of its vascularity, is typically not considered a
target for DBS.
[0043] As described herein, the methods of TMS described may be
used to stimulate multiple sites within a circuit (including
deep-brain sites) in a coordinated fashion. In particular the
method of TMS stimulation described herein may be used to stimulate
one or more targets within a neural circuit to modulate the circuit
and thereby effect a change in the particular indication controlled
by the circuit. For example, in one exemplary neural circuit having
three target sites, LTP or LTD may be achieved. Typically, LTP will
involve higher stimulation powers, synchronous stimulation (hit all
the three targets at the same time), and faster stimulation rates
at all three target sites. LTD, on the other hand, typically might
involve lower stimulation powers, asynchronous stimulation (hit the
three targets at different times), and lower stimulation rates at
the different target sites. The TMS systems and devices described
herein may be used to achieve LTP or LTD in such circuits.
Stereotactic Transcranial Magnetic Stimulation
[0044] Stereotactic Transcranial Magnetic Stimulation (sTMS) may be
used to hit multiple targets using multiple arrays. These arrays
can positively interact in that a coil with one array may
substitute for a coil that would normally occur in another array.
This can be helpful because there physically may not be enough room
for both the single coil serving the two arrays and the coil that
was replaced by that single coil. The multiple targets may be
located at a mixture of deep and superficial locations or may be
all one or the other. The multiple targets may be pulsed
simultaneously or the pulses may be interleaved.
[0045] Techniques that are applicable to multiple-coil arrays used
for Stereotactic Transcranial Magnetic Stimulation (sTMS) include:
[0046] The application of pulse patterns where coils are not
necessarily stimulated simultaneously. [0047] The use of a single
stimulator to energize multiple TMS electromagnets. While typically
each coil is pulsed by a single stimulator, in some cases a single
stimulator may pulse two or more magnets in the same array or in
different arrays. Thus, the number of required stimulators can be
reduced. A different array may be defined as one that is aimed
toward a different target. [0048] sTMS can be accomplished with
sub-Motor-Threshold stimulation at target or higher-powered
stimulation. [0049] Power levels may be adjusted related to depth
of target and patient-specific factors. [0050] Real-time feedback
from patient may be used to modify stimulation parameters including
coil position. [0051] Enhanced perturbations. TMS (sTMS)
Configurations for Clinical Applications
[0052] The treatment of various medical conditions using
Transcranial Magnetic Stimulation as described herein may depend on
the configurations of the electromagnetic coils and how they are
positioned. Exemplary electromagnetic coil configurations
(including arrays of TMS electromagnets) are shown in FIGS. 5-7.
These are not meant to be exclusive. In these figures, the V-coil
and Swept-Wing coils shown as examples were custom developed to
specifications. Such coils may be powered by a stimulator such as
the Magstim Rapid.TM. stimulator, or any other appropriate
stimulator.
[0053] The tables show in FIGS. 8 and 9 illustrate various
exemplary configurations for a selection of clinical applications.
Electromagnetic coil configurations shown represent a selection and
the invention is not limited to these particular configurations.
Other configurations of arrays of TMS electromagnets may be used,
including configurations not described in the examples shown in
FIGS. 5-7.
[0054] Global stimulation, say for Acute Head Trauma, may be
achieved by using a three swept-wing-coil configuration over the
top of the head combined with two swept-wing-coil configurations
placed parallel to it, one located anteriorly over the forehead
aimed inward and the other located posteriorly over the posterior
of the head aimed inward. While generally the targets may be nuclei
or cortical regions, tracts (especially long ones), or a
combination of a non-tract plus a tract (e.g., Orbitofrontal Cortex
combined with the tract between the OFC and the Insula) are
important targets as well. The effectiveness of sTMS on a target
may be increased proportional to the size of the target (e.g., a
bigger target may function as a larger "antenna"). The size of a
target can be effectively increased by including tracts that are
associated with a target, particularly with those providing
connections with associated target structures. Thus non-tracts plus
tracts may offer a larger antenna. A consequence is that if one
has, for example, three interconnected non-tracts, one can have
three non-tract-tract-non-tract target pairs.
[0055] Alternative configurations may be applicable for a given
target, and the selection of which one is used may be dependent on
what other single coils or arrays may be used in the case of
multiple targets being hit for a given clinical application. Both
physical constraints and functional interactions among coils are
applicable and drive the choice, in some cases resulting in a
logical choice among alternatives. Aiming of a given configuration
may also be patient dependent. In some cases, the configuration may
need to be reversed. Targeting a given target, if large, may need
to be more specific for a given application, like superior anterior
Insula for addiction. While a given application might have multiple
targets associated with it, it will not always be desirable to hit
the maximum number of targets possible. Selection of a subset may
reduce undesirable side effects and may be, like drugs, patient
specific. Another consideration is how many TMS stimulators would
be required.
[0056] The triad configurations (in which lateral electromagnets
have their drive currents in opposite polarity to the central coil)
can be used on a patient-specific basis instead of the same
physical configuration where all of the coils have their drive
currents flowing in the same direction.
[0057] Positions of the coils may be determined by using one of
more of atlas (e.g., the Tailarach Atlas used in neurosurgery),
imaging (e.g., PET or fMRI), or tables containing positions of
targets with respect to external landmarks on head.
[0058] The coils may be held in place relative to each other and
positioned relative to the patient's head by coil-fixation devices.
These positions could be positioned manually or robotically. The
manual position could be a cradle with pockets to place the coils
at the correct locations and orientations. In some variations, one
or more coils may be moved to achieve stimulation.
Coil Placements for Addiction, Depression, and Pain
[0059] Three alternatives for coil configurations for Addiction are
included in the table that appears in FIG. 10. As noted, drawings
of these alternatives appear in FIGS. 13, 14, and 15. In all the
references, "right" and "left" refer to the patient's right and
left. In FIG. 13. FIGS. 13-22 show different arrangements and
configurations of TMS electromagnets around a crude simulation of a
patient's head. Alternative 1 employs a single Swept Wing Coil with
its long axis vertical to down-regulate the Insula. In FIG. 14,
Alternative 2, a two Swept-Wing Coil configuration is substituted
supporting deeper penetration of the magnetic field. In FIG. 15,
Alternative 3, four targets are addressed: the Orbito-Frontal
Cortex (OFC), the tract between the OFC and the Insula, the Dorsal
Anterior Cingulate Gyrus (DACG), and the Insula. Alternative 3
involves the stimulation (down regulation) of these four targets,
and because the inclusion of the tract between the Insula and
Orbito-Frontal Cortex, the combination of these three may act as a
large "antenna." The anterior V Coil hits both the OFC and the
tract between the OFC and the Insula. The DACG is stimulated by the
top Swept-Wing Coil and the left V Coil. The Insula is stimulated
by a Swept-Wing Coil on the right. This coil will also function as
part an effective three-coil array by contributing to the
down-regulation stimulation of the DACG. A sub-alternative is the
use of two Swept-Wing Coils on the right to allow for increased
stimulation of the Insula. The level of stimulation can be adjusted
by changing the power applied from the stimulators to any of the
coils.
[0060] Four alternative coil configurations for depression are
included in the table that appears in FIG. 11. As, noted, drawings
of these alternatives appear in FIGS. 16, 17, 18, and 20.
Alternative 1 (FIG. 16) for depression has magnet configurations
with five coils and thus will require five stimulators. In this
alternative, the anterior V Coil is used to down-regulate the Right
Dorso-Lateral Pre-Frontal Cortex (RDLPFC) or up-regulate Left
Dorso-Lateral Pre-Frontal Cortex (LDLPFC). The V-Coil that is
positioned on the anterior right side (where x is on the left in
this case) is used to stimulate the Orbito-Frontal Cortex and the
Subgenual Cingulate. Coils three, four, and five up-regulate the
Dorsal Anterior Cingulate Gyrus. This alternative requires five
stimulators if one coil per stimulator is used. In alternative 2
(FIG. 17), V Coils one and two are configured as in alternative 1,
but only two coils, three and four, are used to up-regulate the
DACG. This permits only four stimulators to be used. In alternative
3 (FIG. 18), the anterior V Coil (Coil 1) stimulates
(down-regulates) the OFC and the Subgenual Cingulate and the
three-coil combination (Coils 2 to 4--two V-Coils lateral to a
central-top Swept-Wing Coil) up-regulate the Dorsal Anterior
Cingulate Gyrus. In alternative 4 (FIG. 19), Coils 2 to 4 are the
same as in alternative 3, but the anterior V-Coil is used to
stimulate the Right or Left Dorsal-Lateral Pre-Frontal Cortex,
involving down-regulating the RDLPFC or up-regulating the LDLPFC.
For the therapy of depression there can be other alternatives, such
as stimulation of both the RDLPFC (Down) and LDLPFC (Up). The
stimulation of the Insula for addition uses the superior anterior
region as the target. Because the Insula has smaller fibers (say
relative to the Dorsal Anterior Cingulate Gyms), the power to be
applied will be greater.
[0061] Three alternatives for coil configurations for treatment of
pain are included in the table that appears in FIG. 12. As, noted,
drawings of these alternatives appear in FIGS. 20, 21, and 22. In
alternative 1 (FIG. 20), the anterior V Coil down regulates the
Cingulate Genu (and will have some impact on the Orbito-Frontal
Cortex as well). The three-coil combination of the top Swept-Wing
Coil flanked by lateral V-Coils down regulate the DACG. In
alternative 2 (FIG. 21), the DACG is stimulated by the top
Swept-Wing Coil and a lateral V-Coil that is placed opposite the
side (X) that the Swept-Wing Coil stimulating the Insula is placed.
The coil hitting the Insula will have impact on the Thalamus on
that side as well. The side X will be patient dependent and may be
related to the side of the pain. In alternative 3 (FIG. 22), the
same configuration as was used in alternative 2 is employed except
that instead of having one Swept-Wing Coil on side X, there are two
Swept-Wing Coils, one hitting the Insula and the other the
Thalamus. Both coils will impact both of the structures to some
extent and both will be impacted more because of the deeper
penetration of the two-Swept-Wing Coil configuration.
General Principles
[0062] In applying TMS methods, devices and systems, any of the
following general concepts may be applied. For example, in general
the TMS systems devices and methods described herein may be
configured for aiming and focusing. [0063] V-Coils can be used to
shape the field of a Swept-Wing Coil (e.g., using two side V-Coils
with current of opposite polarity to a central Swept-Wing Coil will
narrow the magnetic field of that central coil)--this may be called
a "Triad" configuration [0064] If targets are bilateral, and/or if
you need more targets than you can fit magnets in an area, you can
choose to stimulate only one of the bilateral targets. This could
result in hitting one of the targets A from one side and hitting
one of the targets B from other side. In some cases even if the
target appears bilaterally in the brain, only one side is
application to a given clinical application. For example, only the
right Insula is involved in addiction. [0065] In cases where
immediate or close-in-time image feedback is available, e.g., PET
scan looking at Insula as the target, the results may be used to
refine targeting [0066] In cases where immediate or close-in-time
physiologic feedback is available, for example, in acute pain, the
results can be used to refine targeting
Array Packing
[0066] [0067] The number of targets that can be regulated
simultaneously may depend on the ability to physically place the
magnetic coil/magnetic coil arrays [0068] Concentrate on
accommodating the needs of the specific target and create
target-specific coils where needed [0069] Angles and separations
between magnets in array may be target specific [0070] A single
coil or array can be configured to hit more than one target
depending on how the potential targets are aligned [0071]
Incorporate set(s) of coils (up to all the coils for all arrays
focusing on various targets) in a single shell to optimize physical
coil packing [0072] Physically interdigitate coil sets where
appropriate and practical as illustrated by the interdigitation of
figure-8 coils shown in FIG. 23. [0073] A coil in one array can
provide a function that would normally be provided by a coil in
another array (e.g., one of the V-Coils in a Tripled Mixed
Configuration (FIG. 6) in an array can be have one of the V-Coils
removed and its function at least partially provided by a vertical
Swept-Wing Coil in another array as illustrated in the Addiction
configuration in FIG. 15. [0074] Can tie stimulation of coil in one
array to simultaneous stimulation of a coil in another array using
one stimulator instead of requiring two
Substitutions
[0074] [0075] Substitution of TMS electromagnet types (e.g., V-Coil
versus Swept-Wing Coil) may be driven by physical constraints,
and/or power required at the target, and/or wanting to avoid
stimulating other structures. Functional effects can be altered by
increasing or decreasing power applied given that a V-Coil is more
focused but has a weaker magnetic field at a given distance than a
Swept-Wing Coil. Same or Similar Coil Configurations for More than
One Application [0076] The same coils may appear in configurations
for two or more clinical applications, but some or all positions
may be different or the power applied may be different [0077] More
than one application can share the same (set of) configuration(s)
aimed at the same targets but have different up/down regulations
[0078] A common array configuration may neuro-regulate a common
target or set of targets and thus simultaneously treat more than
one clinical application. For example, treatment for both addiction
and depression can be accomplished by simultaneously
down-regulating the DACG and Oribito-Frontal Cortex. In some cases
(e.g., chronically depressed addicts), treating two conditions will
be beneficial to the patient [0079] Even if a common array
configuration is treating more than one clinical application,
treatment for one or both can be facilitated by adding an
additional target that is not common to both applications [0080]
Not all the potential targets for a given condition need to be
regulated to treat that condition, but adding simultaneous targets,
if practical, can improve the results
Stimulation
[0080] [0081] Interleave stimulation of various coil arrays as
appropriate to application [0082] Alternative stimulation
strategies may be applied to reach the same functional end, for
example, depression of neural structures can be accomplished by 1
Hz or lower-frequency stimulation or by theta-burst-pattern
stimulation
[0083] The various embodiments described above are provided by way
of illustration only and should not be construed to limit the
invention. Based on the above discussion and illustrations, those
skilled in the art will readily recognize that various
modifications and changes may be made to the present invention
without strictly following the exemplary embodiments and
applications illustrated and described herein. Such modifications
and changes do not depart from the true spirit and scope of the
present invention.
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